Quantitive cytokine mRNA expression profiles in the colonic mucosa of patients with steroid naïve ulcerative colitis during active and quiescent disease.
BACKGROUND
Cytokines have validated roles in the immunopathogenesis of inflammatory bowel disease (IBD). This study was to investigate the expressions of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-8, and IL-10 mRNAs in the colonic mucosa of patients with ulcerative colitis (UC) during active and quiescent UC.


METHODS
At colonoscopy, biopsies were taken from inflamed and non-inflamed mucosa of patients with steroid-naive UC (n = 15), non-IBD inflammatory colitis controls (ICC, n = 6), and non-colitis controls (NCC, n = 14). The presence of extensive mononuclear cells and neutrophils infiltrate in the lamina propria, cryptitis, and epithelial damage defined an inflammatory lesion in the mucosa. Quantitative cytokine mRNA expressions in biopsies were measured by real-time polymerase chain reaction (PCR).


RESULTS
Of 15 UC patients, 3 remitted with 5-aminosalicylate and 11 received granulocytapheresis; of these, 10 remitted. At baseline, IL-6, IL-8, TNF-alpha, and IL-10 mRNAs were high in inflamed mucosa compared with NCC (P < 0.01). In active UC, IL-6, IL-8 and IL-10 mRNAs were high compared with non-inflamed mucosa (P = 0.03, P = 0.03, P < 0.05, respectively). Both TNF-alpha mRNA (P = 0.03) and IL-6 mRNA (P = 0.04) were higher in UC compared with ICC. Even in non-inflamed mucosa, IL-8 and TNF-alpha mRNA expressions were high compared with NCC. Both IL-6 and IL-8 mRNAs decreased to normal levels after granulocytapheresis.


CONCLUSIONS
During active UC, all 4 cytokine mRNA levels were high; only IL-6 and IL-8 mRNAs decreased to normal levels during remission. IL-8 mRNA was high even at sites of endoscopically quiescent UC during active disease. Steroid naïve patients respond well to granulocytapheresis.
Matsuda
Reikei
R
Department of Internal Medicine, Fujisawa Shounandai Hospital, Fujisawa, Kanagawa, Japan. reikeim@hotmail.com
Koide
Tomoko
T
Tokoro
Chikako
C
Yamamoto
Tsuyoshi
T
Godai
Ten'i
T
Morohashi
Taiki
T
Fujita
Yuji
Y
Takahashi
Daisuke
D
Kawana
Ichiro
I
Suzuki
Shinichiro
S
Umemura
Satoshi
S
D000284:Administration, Oral; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use; D001706:Biopsy; D003093:Colitis, Ulcerative / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D003106:Colon / Q000378:metabolism* / Q000473:pathology; D003113:Colonoscopy; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005786:Gene Expression Regulation; D006098:Granulocytes; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D007937:Leukapheresis / Q000379:methods; D008297:Male; D019804:Mesalamine / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics*; D012074:Remission Induction / Q000379:methods; D012189:Retrospective Studies; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics; D055815:Young Adult
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D015850:Interleukin-6; D016209:Interleukin-8; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019804:Mesalamine